In this study, we show that RPLP1, which is expressed at higher levels in LTNPs compared to RPs, inhibits the transcription of HIV-1 group M subtype B strains that require the transcriptional factor C/EBPβ but not of clade C HIV-1 strains that currently dominate the AIDS pandemic, as well as groups N, O and P. Chromatin immunoprecipitation (ChIP) and DNA binding assays revealed that RPLP1 binds to the C/EBPβ binding sites in the LTR thereby suppressing C/EBPβ binding and consequently viral gene expression. This evidence concerns the gene RPLP1 and AIDS.